反应详情

4-[3-({4-[(5-Chloro-7-iodo-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl]-1-methylpiperazin-2-one (250 mg, 0.40 mmol) and N,N-dimethyl-N′-prop-2-yn-1-ylurea (60 mg, 0.48 mmol) in ethyl acetate (8 ml) stirred at room temperature, under an atmosphere of nitrogen, and treated with bis(triphenylphosphine)palladium(II) dichloride (28 mg, 10 mol %) followed by copper(I) iodide (8 mg, 10 mol %) and diisopropylamine (81 mg, 0.80 mmol). The reaction was stirred 6 hr then DMF (3 ml) added and reaction heated at 60° for 3 hr. A further 60 mg N,N-dimethyl-N′-prop-2-yn-1-ylurea was added and heating continued for 3 hr. The mixture was then evaporated and the residue partitioned between water and dichloromethane. The organic layer was separated, washed with brine, dried over magnesium sulphate and evaporated to an orange oil. This was purified by column chromatography on silica using increasing concentrations of methanol in dichloromethane as eluent to give the title compound (164 mg, 66%) as a pale brown solid; NMR Spectrum:(DMSOd6) 1.99 (quintet, 2H), 2.54 (t, 2H), 2.66 (t, 2H), 2.81 (s, 9H), 3.00 (s, 2H), 3.28 (t, 2H), 3.93 (s, 3H), 4.10 (d, 2H), 4.20 (t, 2H), 6.14 (s, 2H), 6.82 (t, 1H), 7.07 (s, 1H), 7.23 (s(broad), 1H), 7.85 (s, 1H), 8.40 (s(br), 1H), 9.50 (s, 1H); Mass Spectrum: M+H+ 624/626.

1. customreaction
2. temperatureheated at 60° for 3 hr
3. temperatureheating
4. waitcontinued for 3 hr
5. customThe mixture was then evaporated
6. customthe residue partitioned between water and dichloromethane
7. customThe organic layer was separated
8. washwashed with brine
9. dry with materialdried over magnesium sulphate
10. customevaporated to an orange oil
11. customThis was purified by column chromatography on silica using
12. temperatureincreasing concentrations of methanol in dichloromethane as eluent